The therapeutic potential of interleukin-6 in treating obesity

Interleukin (IL)-6 is a multifunctional immune-modulating cytokine that has been suggested to have important functions in glucose and lipid metabolism. It is secreted from adipose tissue during resting conditions and from muscle during strenuous exercise. Recently, the authors reported that mice deficient of IL-6 develop mature-onset obesity, which was reversed by IL-6 replacement. The IL-6-deficient mice had increased glucose levels and decreased glucose tolerance, and blood lipids were increased in females. Furthermore, it was found that intracerebroventricular (ICV) IL-6 treatment acutely increased energy expenditure in rats and led to loss of fat mass following prolonged treatment, without causing symptoms of sickness behaviour or increased levels of acute-phase reactants. Thus, these data indicate a role for IL-6 in the regulation of energy homeostasis in rodents. In humans, several single nucleotide polymorphisms in the IL-6 gene promoter are known, one of which (174 C) is associated with reduced IL-6 transcription as well as decreased basal metabolic rate and insulin sensitivity in healthy male subjects. Furthermore, it was found that IL-6 levels in cerebrospinal fluid in obese humans were inversely correlated with more severe obesity, suggesting that severe obesity is coupled to a relative central IL-6 deficiency. Taken together, these data suggest that endogenous IL-6 has antiobesity effects and, therefore, it is possible that low endogenous IL-6 production contributes to obesity in humans.